Technical Abstract:
Elucidation of the association between total plasma homocysteine (tHcy) levels and risk for atherosclerosis has important implications for the prevention of cardiovascular disease (CVD). We used data from the Vitamin E Atherosclerosis Prevention Study (VEAPS), a double-blind, placebo- controlled trial, to examine the relationship between gender, hormone replacement therapy (HRT), tHcy levels, and common carotid artery (CCA) intima-media thickness (IMT) in 351 asymptomatic men (n=167) and women (n=184) >/-45 years old. tHcy levels (mean +/- standard error) were lower in women than men (7.03+/-0.15 vs. 7.99+/-0.18 nmol/ml, p=0.0001) and correlated with baseline CCA IMT in both women (r=0.18, p=0.01) and men (r=0.15, p=0.05). tHcy levels were nonsignificantly lower in current HRT users (n=71) than non-users (n=113) but were significantly lower in women with long-term HRT use of >/-7 years (n=35) compared with all other women (n=149), 6.21+/-0.33 vs. 7.23+/-0.16 nmol/ml, p=0.006. tHcy levels were correlated with CCA IMT (r=0.27, p=0.007, n=149) in women who used HRT for <7 years but were not correlated in those who used HRT for >/-7 years. In HRT non-users, quartile analysis indicated that mean CCA IMT was 0.72 mm among tHcy levels up to 8.47 nmol/ml and 0.82 mm at >/-8.48 nmol/ml (p=0.05); there was no trend in current HRT users. In women with <7 years HRT use, mean CCA IMT was 0.72 mm among tHcy levels up to 8.47 nmol/ml and 0.81 mm at >/-8.48 nmol/ml (p=0.03); there was no trend in women with HRT use >/-7 years. These data indicate that tHcy levels are lower in women than men and that HRT, especially long-term HRT use, may play in important role in lowering tHcy levels. These findings suggest one possible mechanism by which HRT may exert its protection for CVD.